JM Montserrat

CHEYNE‐STOKES, APNEAS COMPLEJAS Y 

CENTRALES USO DE LA VENTILACIÓN 

SERVO

1. Introducción

2. Apneas

3. Servo ventilación

1. Introducción

2. Apneas

3. Servo ventilación

UPPER AIRWAYPATENCY /COLLAPSE

UPPER AIRWAY FACTORS: (+)

ANATOMIC Obesity, retrognatia…

COLAPSABILYTYShapeTissue properties

BRAIN STEMCENTERS

Upper airway mechanoreceptorsNegative pressureVibration

UPPER AIRWAYMUSCLES (-)

Apnea

1

2

Dempsey et  al. Pathophysiology of Sleep Apnea. Physiol Rev  2010; 47–112

UPPER AIRWAYPATENCY /COLLAPSE

UPPER AIRWAY FACTORS: (+)

ANATOMIC Obesity, retrognatia…

COLAPSABILYTYShapeTissue properties

BRAIN STEMCENTERS

Upper airway mechanoreceptorsNegative pressureVibration

UPPER AIRWAYMUSCLES (-)

Apnea

1

2

Pes

(cm

H2O

)ǀZǀ(

cmH

2O*s

/l)

-15

50

V’ (

l/s)

-1

1

0

20

0

Kimoff et al 2009.

1. Introducción

2. Apneas

3. Servo ventilación

1. No  Pueden• Obstructivas

2. No  Quieren• Centrales

3. Patrón Respiratorio Irregular• Cheyne‐ Stokes, Apnea compleja

LAS OBSTRUCTIVAS

Large negative intrathoracic pressures

CARDIAC OVERLOAD

Oxidative stress

Systemic inflammation

Endothelial dysfunction

Adipokines

Hypertensión

Metabolic disturbances

Arteriosclerosis

Large negative intrathoracic pressures

Fragmented and non-restorative sleep(somnolence, cognitive..)

Caples 2005. Modified

OBESIDAD

CARDIOVASCULAR

SAHS

Intermittent air

CIH highHigh cholesterol diet

Intermittent airHigh cholesterol diet

CIH

Mice exposed to CIH and high-cholesterol diet developed atherosclerotic lesions in the aortic origin and descending aorta. 4 weeks (cross-sections of the aortic origin, using oil red O stain)

Vladimir Savransky. AJRCCM 2007

1. No  Pueden• Obstructivas

2. No  Quieren• Centrales

3. Patrón Respiratorio Irregular• Cheyne‐ Stokes, Apnea compleja

CLASSIFICATION OF CENTRAL APNEAS

• In hypercapnic subjects:- neurologic or muscle deficits

• In hypocapnic or normocapnic subjects:

- instability of the respiratory drive

• Other central apneas

M S Badr. Prim Care Clin Office Pract. 2005: 361–374

Complex sleep apnea and obesity hypoventilation syndrome opposite ends of the spectrum of OSA?

Marrone, Med Hypoth 2009

Hypoventilation(OHS)

Central Apneas(Complex)

1. No  Pueden• Obstructivas

2. No  Quieren• Centrales

3. Patrón Respiratorio Irregular• Cheyne‐ Stokes, Apnea compleja

LAS CHEYNE‐STOKES

Cheyne, J.

“A case of Apoplexy, in Which the Fleshy Part of the Heart Was Converted into Fat.”

Dublin Hospital Reports, 1818, II, 216.

“…For several days his breathing was irregular; it would entirely cease for a quarter of minute, then it would become perceptible, though very low, then by

degrees it became heaving and quick, and then it would gradually cease again: this revolution in the state of his breathing occupied about a minute during which

there were about thirty acts of respiration...”

Stokes, W.

“Observations on some Cases of permanently slow Pulse.”Dublin Quart. Jour. Med. Sc.,1846,II,83.

“…Then a very feeble, indeed barely perceptible inspiration would take place, followed by another somewhat stronger, until at length high heaving, and even violent breathing was established, which would then subside till the next period of suspension… This was frequently a quarter of minute in duration

. I have little doubt that this was a case of weakened and probably fatty heart, with disease of the aorta…”

…of a patient with probable cardiac asthma:60 sec.

0 1 2 3 4 5 6 7 8 9 10

30 sec.

PREVALENCIA OSA EN LA INSUFICIENCIA CARDIACA

Does CSR worsen prognosis in CHF patients?

Yumino and Bradley: Cheyne‐Stokes Respiration with Central Sleep Apnea

Proc Am Thorac Soc, 2008

central apnea

Xie et al., AJRCCM 1994;150:489-95

PCO2 belowapnea threshold

Awakeventilation

NREM

transition

IncreasingPCO2

ventilation

arousal

Highventilatory responseto CO2

++

++

Regular non-REM ventilation

PCO2 aboveapnea threshold

Sin et al. Circulation, 2000

Heart-Transplantation-free Survival

Bradley, T. et al. N Engl J Med 2005

CANPAP: Survival Analysis

No effect of CPAP on survival in CHF+CSA (CanPAP) Bradley et al. N Engl J Med 2005; 353: 2025-2033

Post-hoc analysisArtz et al. Circulation 2007; 115: 3173-3180

OSA  EN LA INSUFICIENCIA CARDIACAMOTIVOS PARA CONSIDERAR SU TRATAMIENTO

HIPOXIA Y AROUSALS: Activación simpática, inflamación

SUEÑO FRAGMENTADO:Activación simpática, cansancio diurno p, posa 

somnolencia

MAYOR MORTALIDAD  Y MORBILIDAD: ?

DETERIORO MAS RÁPIDO DE LA INSUF. CARDIACA: ?

1. No  Pueden• Obstructivas

2. No  Quieren• Centrales

3. Patrón Respiratorio Irregular• Cheyne‐ Stokes, Apnea compleja

Complex apnea is defined by the 

development of central apnea in the OSA 

patient during the initial CPAP titration.

(treatment‐emergent central apnea) 

COMPLEX SLEEP APNEAAt diagnosis: OSAS

During CPAP: obstructive events abolished, But:

central apnea index ≥5 or large amount of periodic breathing

Breakpoint: CPAP level above which respiratory periodism worsens or central apneas appear

Natural history of CompSA in OSA patientsJavaheri et al. J Clin Sleep Med 2009; 5: 205-211

• Retrospective analysis on over 1200 OSA patients

• Prevalence estimated at 6.5%

• AHI on CPAP decreased over time, but did not normalize in 1.5% of patients

• Risk factors for persistent CSA:– Severe OSA – High central apnea index at diagnosis– Use of opioids

Study Intervention n Duration Results

Artz et al, Chest 2008

Acute CPAP or BiPAP vs flow-triggered ASV

14 CHF 2 nights ↓ AHI, flow-triggered ASV well tolerated

Randerath et al, Sleep Med 2008

Flow-triggered ASV

10 (6 CHF)

8 weeks ↓ AHI and arousals in pts with and without CHF

Kasai et al, Circ Heart Fail 2010

RCT flow-triggered ASV vs CPAP

31 CHF 3 months Better results in flow-triggered ASV group(↓ AHI, ↑ LVEF, QoL and compliance)

Studies on flow-triggered ASVin CHF patients with OSA+CSR

EPAP = 4 cm H2OIPAPmin = EPAP

IPAPmax = IPAPmin + 10 cm H2OAutomatic back-up rate

Obstructive events

Central Apneas

Continued PB pattern

Final setting

No

No

No

Yes

Yes

Yes

EPAP ↑ by 1 cmH2O (up to 10)

Back-up rate ≥10 breaths/min

IPAP max ↑ by 2 cmH2O

Flow-triggered ASV (dynamic BiPAP):

Titration

Kasai et al. Circ Heart Fail 2010; 3: 140-148

Studies on ASV in CHF patientsStudy Intervention n Duration Results

Pepperell et al, 2003

RCT ASV therapeutic vs subtherapeutic

39 CHF-CSR

1 month ↓ sleepiness, AHI, BNP, urinary catechol. in therapeutic ASV group

Philippe et al, 2006

RCT CPAP vs ASV 25 CHF-CSR

6 months ↓ AHI, ↑ LVEF, better compliance and QoL in ASV group

Fietze et al, 2008

RCT BiPAP S/T vs ASV

39CHF-CSR

6 weeks ↓ AHI, ↑ LVEF in both groups

Hastings et al, 2010

ASV vs no ventilatory treatment (declined ASV)

19 CHF-CSR

6 months ↓ AHI, ↑ LVEF, ↑ QoL, BNP= in ASV group

Koyama et al, 2010

ASV vs no ventilatory treatment (declined ASV)

17 CHF-CSR

4 weeks ↓ AHI, ↓ BNP, ↓hsCRP in ASV group

Patient Characteristics

• > 90% are Male•• BMI is slightly less than average OSA    patient? 

• Higher incidence of ischemic heart disease or CHF Prevalence of 10‐15% in OSA Patients

Polysomnographic Characteristics

May have evidence of central events on baseline PSG

Events more common in nREM sleepElevated Arousal Index

Possible Reduction in Central Events on future follow‐up

Clinical Impact of nCPAP in “Complex Apnea”

Residual or Worsening Symptoms  (Fatigue, EDS, Depression)

Secondary to Arousals/Disrupted Sleep

Higher Incidence of “CPAP Difficulty” ↑  Sympathetic Activity?  of ↑ Mortality

COMPLEX SLEEP APNEA

Definition of Complex Sleep Apnea

Causes of Central Apnea Developing on CPAP Therapy

Treatment Options

Implications of the Syndrome

COMPLEX SLEEP APNEA

Definition of Complex Sleep Apnea

Causes of Central Apnea Developing on CPAP Therapy

Treatment Options

Implications of the Syndrome

Treatment Considerations in Complex Apnea

1. Increase CO2 Reserve ValueA. ? O2 

B. ? Induce AcidemiaC. Increase Dead Space

2. Reduce Loop GainA. Treat CHFB. ? Sedatives

3. Provide Back‐UpA. Backup Rate on Therapy

Treatment OptionsnCPAP with Permissive Flow Limitation

Supplemental O2 

MedicationsAcetazolamideTheophyllineBenzodiazepines

Additional Dead Space to nCPAP

Positive Airway Pressure Gas Modulation

Adaptive Servo Ventilation (ASV)

Implications1. To OSA Patient

15% will not respond to nCPAP

Cost of Alternative Therapies may be Prohibitive

2. To Sleep Centers

Responsibility to Identify such patients and offer Treatment Modifications

3. To Sleep Medicine Society

Consider Consequences in Offering Home Studies (Non‐Titrated) as well as Automated CPAP

Future Questions and Goals

Clarify Definition and Natural History of Complex Sleep Apnea

Improve Identification Process of At‐Risk Patient

Improvement in Technology Utilized in making the Diagnosis

Develop Treatment Options that are Cost‐Effective

1. Introducción

2. Apneas

3. Servo ventilación

Adaptive Pressure Support Servo‐ventilation (APPSV)

Untreated Cheyne‐Stokes Respiration Treated Cheyne‐Stokes Respiration

Teschler; AJRCCM 2001

OBJETIVOEstabilizar la ventilación  (C‐S y suprimir el “open loop”)

METODOLOGÍAMedir la ventilación previa of  basal o la que supuestamente  tiene el individuo

Valorar si las apneas son centrales u obstructivas

Si son obstructivas aumentar el EPAP

Si son centrales aumentar la IPAP de un modo sincronizado

Confort del paciente

RESULTADOS FINALES A ALCANZARMejorar la calidad de vida, morbilidad y mortalidad

Estimar la ventilación basal del paciente

Análisis de los 1-4 minutos previos

Mantener las ventilación

estimada durante el sueño

D Navajas AJRCCM 1998

D Navajas AJRCCM 1998

5 cm H2O

6 cm H2O

Pressure Settings

•EPAPMIN = 4 cm H2O, EPAPMAX =15 cm H2O 

•PS MIN = 0 cm H2O, PS MAX = 15 cm H2O 

•Maximum (IPAP) pressure, P MAX =25 cm H2O 

•Back‐up rate : Auto 

•Bi‐Flex : OFF 

•Alarms: All must be disabled 

Effectiveness of Different Therapies in CSA

Teschler H et. al; AJRCCM 2001

C. Philippe et al., Heart 2006;92:337

ASV vs. CPAP for CSA in HF

* p <0.05

**

*

*

Los  trabajos iníciales siguieren su utilidad

Hacen falta mas estudios con una población mas amplia  dirigidos no solo a si el equipo funciona bien o no, sino si reduce la comorbilidad y mortalidad

No existen trabajos negativos Equipos sofisticados

Es  imprescindible  exigir  a la empresas equipos robustos mas que excesivamente superinteligentes

MIS CONCLUSIONES

La titulación es probablemente  imprescindible

No  todos lo pacientes van a adaptarse  inicialmente  y  pueden requerir varios estudios

Entreno educación a los pacientes y médicos es completamente necesaria 

Los  ASV no  deben  de ser utilizados como  “black box”

MIS CONCLUSIONES